During infection viruses hijack host cell metabolism to promote their replication. Here, analysis of metabolite alterations in macrophages exposed to poly I:C recognises that the antiviral effector Protein Kinase RNA-activated (PKR) suppresses glucose breakdown within the pentose phosphate pathway (PPP). This pathway runs parallel to central glycolysis and is critical to producing NADPH and pentose precursors for nucleotides.
View Article and Find Full Text PDFWe present compelling evidence for the existence of an extended innate viperin-dependent pathway, which provides crucial evidence for an adaptive response to viral agents, such as SARS-CoV-2. We show the in vivo biosynthesis of a family of novel endogenous cytosine metabolites with potential antiviral activities. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy revealed a characteristic spin-system motif, indicating the presence of an extended panel of urinary metabolites during the acute viral replication phase.
View Article and Find Full Text PDFOver 70 million people are currently at risk of developing Chagas Disease (CD) infection, with more than 8 million people already infected worldwide. Current treatments are limited and innovative therapies are required. , the etiological agent of CD, is a purine auxotroph that relies on phosphoribosyltransferases to salvage purine bases from their hosts for the formation of purine nucleoside monophosphates.
View Article and Find Full Text PDFhypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) is essential for purine salvage of hypoxanthine into parasite purine nucleotides. Transition state analogue inhibitors of HGXPRT are characterized by kinetic analysis, thermodynamic parameters, and X-ray crystal structures. Compound , 9-deazaguanine linked to an acyclic ribocation phosphonate mimic, shows a kinetic of 0.
View Article and Find Full Text PDFAm J Speech Lang Pathol
November 2022
Purpose: Two disparate models drive American speech-language pathologists' views of evidence-based practice (EBP): the American Speech-Language-Hearing Association's (2004a, 2004b) and Dollaghan's (2007). These models discuss evidence derived from clinical practice but differ in the terms used, the definitions, and discussions of its role. These concepts, which we unify as , are an important part of EBP but lack consistent terminology and clear definitions in the literature.
View Article and Find Full Text PDFChagas disease, caused by the parasitic protozoan , affects over 8 million people worldwide. Current antiparasitic treatments for Chagas disease are ineffective in treating advanced, chronic stages of the disease, and are noted for their toxicity. Like most parasitic protozoa, is unable to synthesize purines , and relies on the salvage of preformed purines from the host.
View Article and Find Full Text PDFStereoselective total syntheses of the four stereoisomeric forms of guaiacylglycerol 8--4'-coniferyl ether, viz., compounds , -, , and -, have been established. The key step involves an Evans/Seebach auxiliary-controlled and syn-selective aldol process followed, in the reaction sequences leading to the anti-compounds, by a Mitsunobu reaction involving a benzylic alcohol residue.
View Article and Find Full Text PDFThe title compounds of the general form 1 can be produced at large scale and in essentially enantiomerically pure form (when X≠H) through the whole cell biotransformation of the corresponding aromatic. The "dense" and varied functionality associated with these metabolites mean that they have become increasingly useful chirons for the total synthesis of a range of natural product types. This personal account details the outcomes of a nearly three-decade long campaign within our group to exploit these compounds in the synthesis of a diverse range of small molecule natural product targets.
View Article and Find Full Text PDFA total synthesis of compound 3 from d-(-)-tartaric acid is reported, thereby establishing that the structure, including relative stereochemistry, originally assigned to the cyclic carbonate-containing natural product aspergillusol B is correct.
View Article and Find Full Text PDFSyntheses of certain di- and mono-oxygenated derivatives (e.g., 2 and 3, respectively) and analogues (e.
View Article and Find Full Text PDFThe aquatic food web of the Great Lakes has been contaminated with polychlorinated biphenyls (PCBs) since the mid-20th century. Threats of PCB exposures to long-lived species of fish, such as lake sturgeon (Acipenser fulvescens), have been uncertain because of a lack of information on the relative sensitivity of the species. The objective of the present study was to evaluate the sensitivity of early-life stage lake sturgeon to 3,3',4,4',5-pentachlorobiphenyl (PCB-126) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.
View Article and Find Full Text PDFA1 Preterm and low birth weight nutrition in the first month life: implications for the outcome Massimo Agosti A2 Behind human milk and breastfeeding: not only food, not only growth Carlo Agostoni A3 To prevent obesity: importance and issues of cultural adaptation from weaning to 3 years of age Serge Chalons A4 Diet before and during pregnancy and child health: lessons from animal models Pascale Chavatte-Palmer A5 Infant nutrition: an opportunity to optimize future health José Manuel Moreno Villares A6 Complementary feeding strategies to facilitate acceptance of fruits and vegetables Sophie Nicklaus A7 Diet of young children in the Mediterranean region Luís Pereira-da-Silva A8 Proposal of 10 good practices to help prevent obesity in the first 1,000 days Angelo Pietrobelli, the MeNu Group A9 Macronutrient intakes in early life and subsequent risk of obesity Marie Françoise Rolland-Cachera A10 The burden of childhood obesity in Italy and the results of Nutrintake study Gian Vincenzo Zuccotti A11 Growth body composition and growth hormone therapy: linear growth Marco Cappa A12 Early nutrition pattern and late metabolic consequences Manuela Caruso-Nicoletti A13 Nutrition and Insulin-like Growth Factor (IGF) System Elena Inzaghi, Stefano Cianfarani A14 Nutrition of preterm infants Mario De Curtis A15 Early nutrition patterns and later metabolic outcomes- I part: Genetic and metabolic mechanisms Laura Guazzarotti A16 Diagnosis of metabolic disease by imaging techniques Lorenzo Iughetti A17 Nutrition, growth and cardiovascular diseases Francesco Chiarelli, Laura Comegna, Simone Franchini A18 Body fat mass and gender Laura Perrone, Giuseppina Rosaria Umano A19 Lifestyle interventions for an appropriate birth weight Elisabetta Petrella, Raffaele Bruno, Valentina Bertarini, Giulia Pedrielli, Isabella Neri, Fabio Facchinetti A20 Nutrition, growth and body composition Flavia Prodam A21 Nation-specific reference growth charts in the daily practice Alessandro Sartorio, John M. H. Buckler, Nicoletta Marazzi A22 Growth patterns in inflammatory bowel diseases (IBD) and in cystic fibrosis (CF) Maria E.
View Article and Find Full Text PDFConcern exists that polychlorinated biphenyls (PCBs) may be contributing to the current decline of shovelnose sturgeon (Scaphirhynchus platorynchus) and the US federally endangered pallid sturgeon (Scaphirhynchus albus). Waterborne exposures with newly fertilized eggs were used to assess developmental and morphological effects of 2 of the most potent aryl hydrocarbon receptor (AhR) agonists, 3,3',4,4',5-pentachlorobiphenyl (PCB-126) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on early life stage shovelnose and pallid sturgeon. No dose-related effects of PCB-126 were observed on percent development or hatch in either species at concentrations as high as 1711 ng/g egg.
View Article and Find Full Text PDFUnlabelled: The incidence of pubic lice infestations is estimated to be between 1.3% and 4.6%, with an average incidence of 2% worldwide.
View Article and Find Full Text PDFExpression of atheroprotective genes in the blood vessel wall is potentially an effective means of preventing or reversing atherosclerosis. Development of this approach has been hampered by lack of a suitable gene-transfer vector. We used a helper-dependent adenoviral (HDAd) vector to test whether expression of apolipoprotein A-I (apoA-I) in the artery wall could retard the development of atherosclerosis in hyperlipidemic rabbits.
View Article and Find Full Text PDFThe success of gene therapy hinges on achievement of adequate transgene expression. To ensure high transgene expression, many gene-therapy vectors include highly active virus-derived transcriptional elements. Other vectors include tissue-specific eukaryotic transcriptional elements, intended to limit transgene expression to specific cell types, avoid toxicity and prevent immune responses.
View Article and Find Full Text PDFBackground: Few studies have compared the growth of a twin with its co-twin and particularly in relation to birth weight discordance.
Aim: The study investigated how the degree of birth weight discordance affected subsequent growth.
Methods: Birth weight discordance of 762 twin pairs was determined.
Arterial endothelial cells (EC) are attractive targets for gene therapy of atherosclerosis because they are accessible to hematogenous and catheter-based vector delivery and overlie atherosclerotic plaques. Vector-mediated expression-in EC-of proteins that mediate cholesterol transfer out of the artery wall and decrease inflammation could prevent and reverse atherosclerosis. However, clinical application of this strategy is limited by lack of a suitable gene-transfer vector.
View Article and Find Full Text PDFUrokinase-type plasminogen activator (uPA) is expressed at increased levels in stenotic, atherosclerotic human arteries. However, the biological roles of uPA in the artery wall are poorly understood. Previous studies associate uPA with both acute vasoconstriction and chronic vascular remodeling and attribute uPA-mediated vasoconstriction to the kringle - not the catalytic - domain of uPA.
View Article and Find Full Text PDFN Am J Sports Phys Ther
November 2009
Background: Conflicting reports of range of motion (ROM) findings exist related to shoulder instability. Knowledge of range of motion findings among individuals with shoulder subluxation may aid in diagnosis and facilitate appropriate management.
Purpose: The purpose of this study was to compare passive rotation ROM and determine if a symptom-provoking activity alters ROM between patients with shoulder subluxations and healthy controls.
Background: Size at birth has an important relationship to subsequent growth. Many reports subgroup subjects according to birth weight or birth weight in relation to the duration of gestation, and it is not clear whether one of these methods is more relevant to subsequent growth or if in fact they are comparable.
Aim: The present study compared the outcome of twins in terms of pre-pubertal weight and height when sub-grouped according to birth weight (BW), or the appropriateness of birth weight for the duration of gestation (BW-SDS).
The phosphoinositide 3-kinase (PI3K) signaling pathway plays a critical role in the development, activation, and homeostasis of T cells by modulating the expression of survival and mitogenic factors in response to a variety of stimuli. Ligation of the antigen receptor, costimulatory molecules, and cytokine receptors activate PI3K, resulting in the production of the lipid second messenger phosphatidylinositol-3,4,5-triphosphate (PIP(3)). A number of molecules help to regulate the activity of this pathway, including the lipid phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10).
View Article and Find Full Text PDFThis case report describes the outcomes of a method of constraint-induced movement therapy (CIMT) incorporated into a home program using a minimally restrictive constraint over an 18-month period. The movement of the uninvolved hand and wrist of a 13-month-old child with hemiparesis was constrained with a soft removable mitt. Caregivers performed CIMT in 2 intense periods and weaning periods, and a home exercise period.
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